dapagliflozin/ metformin/saxagliptin           

Action and Spectrum

Actions and Spectrum 

dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that reduces renal glucose reabsorption, thereby increasing urinary glucose excretion and reducing plasma glucose levels. saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that inhibits the degradation of incretin hormones, which results in increased insulin secretion and decreased glucagon secretion. metformin is a biguanide that decreases hepatic glucose production and enhances insulin sensitivity in peripheral tissues. 

Combined, these three medications exert complementary effects on glucose metabolism, improving glycemic control. The combination of dapagliflozin, saxagliptin, and metformin has a broad spectrum of activity and is indicated for treating adult patients with type 2 diabetes mellitus who have inadequate glycemic control with metformin or saxagliptin alone, or who are already treated with the combination of dapagliflozin and metformin. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

Genital infection (3%) 

Arthralgia (2.4%) 

Diarrhea (3.7%) 

Dyslipidemia (5.1%) 

Urinary tract infection (5.7%) 

Headache (4.3%) 

Back pain (3.3%) 

Postmarketing Reports 

Dapagliflozin  

Rash 

Ketoacidosis 

Urosepsis 

Renal impairment 

Acute kidney injury 

Pyelonephritis 

Saxagliptin  

Hypersensitivity reactions including angioedema anaphylaxis and exfoliative skin conditions 

Severe and disabling arthralgia 

Rhabdomyolysis 

Pancreatitis 

Bullous pemphigoid 

Metformin 

mixed hepatocellular liver injury 

Cholestatic  

hepatocellular 

Black Box Warning

Black Box Warning:  

Lactic acidosis 

Contraindication / Caution

Contraindication/Caution: Hypersensitivity: Patients with a known hypersensitivity or allergy to dapagliflozin/ metformin/saxagliptin should avoid using this medication. 

Renal impairment: The drug should not be used in patients with renal impairment due to the increased risk of lactic acidosis.  

Severe hepatic impairment: Patients with severe hepatic impairment, defined as a Child-Pugh score of 10 or greater, should avoid using this medication due to the risk of lactic acidosis.  

Metabolic acidosis: The drug should not be used in patients with metabolic acidosis, including diabetic ketoacidosis (DKA), due to the potential for exacerbating acidosis. 

Alcohol intoxication: Patients who are intoxicated with alcohol due to the increased risk of lactic acidosis. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excreted into human milk is unknown 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

The drug is a fixed-dose combination medication used to manage type 2 diabetes mellitus. The medication contains three active ingredients: dapagliflozin/ metformin/saxagliptin 

Pharmacodynamics:  

dapagliflozin is an SGLT2 inhibitor that reduces renal glucose reabsorption, leading to increased glucose excretion in the urine. saxagliptin is a DPP-4 inhibitor that enhances the action of incretin hormones, which increase insulin secretion and reduce glucagon secretion. metformin, on the other hand, decreases hepatic glucose production, increases peripheral glucose uptake, and reduces intestinal glucose absorption. 

Pharmacokinetics: 

Absorption 

 The absorption of the drug occurs primarily in the small intestine. dapagliflozin is absorbed with a median Tmax of 2 hours. saxagliptin is rapidly absorbed with a Tmax of 2 hours. metformin is absorbed with a Tmax of 2.5 hours. 

Distribution 

 The drug has a moderate volume of distribution. dapagliflozin and saxagliptin are highly protein-bound with a plasma protein binding of >90%. metformin is minimally protein-bound. 

Metabolism 

The metabolism of the drug take place in liver and kidney. dapagliflozin is primarily metabolized by UGT1A9 and UGT2B7. saxagliptin is metabolized in the liver by CYP3A4/5 and CYP2C8. metformin is not metabolized and is eliminated unchanged in the urine  

Excretion and Elimination dapagliflozin/ metformin/saxagliptin is eliminated primarily by the kidney. dapagliflozin is eliminated with a half-life of approximately 12.9 hours. saxagliptin is eliminated with a half-life of approximately 2.5 hours. metformin is eliminated with a half-life of approximately 2-6 hours. 

Adminstartion

Administration:   

dapagliflozin/ metformin/saxagliptin should be taken orally with a meal at the recommended starting dose of one tablet twice daily.  

Patients should take the medication simultaneously each day and swallow the tablets whole. 

Patient Information Leaflet

Patient information leaflet 

Generic name: dapagliflozin/ metformin/saxagliptin 

Why do we use dapagliflozin/ metformin/saxagliptin?  

dapagliflozin/ metformin/saxagliptin is a combination medication used to manage blood sugar levels in individuals with type 2 diabetes.